血清miR-424及miR-765在多发性骨髓瘤中的表达及其临床意义

Expression and Clinical Significance of Serum MiR-424 and MiR-765 in Multiple Myeloma

目的:探讨多发性骨髓瘤(MM)患者血清miR-424及miR-765的表达及其临床意义。方法:选取2017年1月-2020年7月三亚中心医院收治的81例MM患者,依据国际分期系统分为Ⅰ期(n=16)、Ⅱ期(n=25)和Ⅲ期(n=40);根据免疫分型结果分为IgG型(n=46)、IgA型(n=19)、轻链型(n=10)和非分泌型(n=6)。另选取同期50例健康体检正常者作为对照组。检测各组血清miR-424、miR-765及胱抑素C(Cys-C)水平。应用受试者工作特征(ROC)曲线分析血清miR-424、miR-765及Cys-C水平诊断MM的价值。采用Pearson相关分析MM患者血清miR-424、miR-765水平与Cys-C的相关性。结果:MM组血清miR-424(2.74±1.30 vs 0.85±0.26)、miR-765(2.05±0.82 vs 0.63±0.17)及Cys-C[(2.18±0.86 vs 0.72±0.15)mg/L]水平均明显高于对照组(P<0.001)。MMⅢ期患者血清miR-424(5.08±2.36 vs 1.12±0.34,2.24±0.93)、miR-765(3.50±1.52 vs 0.74±0.20,1.78±0.65)及Cys-C[(3.81±1.30 vs 0.92±0.24,1.68±0.55) mg/L]水平均明显高于Ⅰ期和Ⅱ期(P<0.001),且Ⅱ期患者血清miR-424、miR-765及Cys-C水平均明显高于Ⅰ期(P<0.001)。MM IgG型患者血清miR-424及miR-765水平均明显高于IgA、轻链和非分泌型(P<0.001)。ROC曲线分析结果显示,miR-424、miR-765、Cys-C及3项联合诊断MM的曲线下面积以后者为最大(0.952,95%CI:0.890-0.993),其敏感度和特异度为95.0%和87.2%。相关分析结果显示,MM患者血清miR-424及miR-765水平与Cys-C均呈正相关(r=0.795,r=0.760)。结论:MM患者血清miR-424及miR-765水平明显升高,且随着MM病情分期呈增高趋势,联合Cys-C检测对MM诊断具有较高的价值。

Objective: To investigate the expression and clinical significance of miR-424 and miR-765 in patients with multiple myeloma(MM). Methods: The eighty-one MM patients admitted to Sanya Central Hospital from January 2017 to July 2020 were divided into phase Ⅰ(n=16), phase Ⅱ(n=25) and phase Ⅲ(n=40) according to the international staging system, while they were divided into IgG type(n=46), IgA type(n=19), light chain type(n=10) and non secretory type(n=6) according to the results of immunotyping. Another 50 healthy normal persons in the same period were selected as the control group. The levels of serum miR-424, miR-765 and Cystatin C(Cys-C) were measured in each group. The diagnostic value of serum miR-424, miR-765 and Cys-C in MM was estimated by ROC curve. Pearson correlation was used to analyze the correlation between serum levels of miR-424, miR-765 and Cys-C in MM patients. Results: The serum levels of miR-424(2.74±1.30 vs 0.85±0.26), miR-765(2.05±0.82 vs 0.63±0.17) and Cys-C [(2.18±0.86 vs 0.72±0.15) mg/L] in MM group were significantly higher than those in control group(P<0.001). The serum levels of miR-424(5.08±2.36 vs 1.12±0.34, 2.24±0.93), miR-765(3.50±1.52 vs 0.74±0.20, 1.78±0.65) and Cys-C [(3.81±1.30 vs 0.92±0.24, 1.68±0.55) mg/L] in MM patients at stage Ⅲ were significantly higher than those in patients at stage Ⅰ and Ⅱ(P<0.001). Also the serum levels of the three molecules in phase II w ere significantly higher than those in phase I( P < 0. 001). The serum levels of miR-424 and miR-765 in MM patients at Ig G type w ere significantly higher than those at Ig A,light chain and non secretory types( P< 0. 001). ROC curve analysis show ed that the area under the curve( 0. 952,95% CI: 0. 890-0. 993) was greatest for the combination of miR-424,miR-765 and Cys-C for diagnosis of M M,and its sensitivity and specificity w ere 95. 0%and 87. 2%. The results of correlation analysis show ed that the serum levels of miR-424 and miR-765 were positively correlated w ith Cys-C( r = 0. 795,r = 0. 760). Conclusion: The serum levels of miR-424 and miR-765 in M M patients are significantly increased in the pattern increasing with the progression of MM stage. Combined w ith Cys-C,miR-424 and miR-765 have high value in the diagnosis of MM.